Sialic acids (NeuAc) and its derivatives are found on cell membranes and in body fluids in all mammals and many higher-order animals, as well as pathogenic microorganisms. Based on an understanding of the biosynthesis of sialic acid and the evolving elucidation of the genomes of multiple microbes, researchers have described at least four mechanisms of microbial surface sialylation. These include de novo synthesis, donor scavenging, trans-sialylation and precursor scavenging. To understand the role of sialic acids in pathogenesis, it is important to examine their role in eukaryotic systems. Sialic acid-dependent receptors play an important role in adhesion to mammalian cells. Two examples of the receptors, the selectin and sialoadhesin families, are discussed in this chapter. There is a correlation between sialic acid levels and the development of cancer. A tumor cell has an increased amount of sialylation and sialyltransferase activity. The biological effects of sialylation, which mediate antiphagocytosis, anticomplement activity, and protection against bactericidal killing, have the potential to act with sialic acid binding immunoglobulinlike lectins (siglecs) on the surface of hematopoietic and immune system cells. Many bacteria produce neuraminidases, which can modify the sialylation of microbial and human tissues. Bacterial biofilms and their role in pathogenicity have generated considerable interest because of their role in antimicrobial resistance and pathogenesis. Recent studies demonstrating the potential for cooperative behavior between bacteria suggest that in complex communities, the disadvantages of surface sialylation may be obviated by neuraminidase production by a neighboring microbial partner.

The nine-carbon structure of N-acetylneuraminic acid. Natural substitutions of the basic structure result in over 40 different compounds. Recently, studies of unnatural substitutions have suggested possible innovative approaches to the treatment of a number of human diseases (11, 12, 53, 88).

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10.1128/9781555817619/fig6-1.gif

Figure 1

The nine-carbon structure of N-acetylneuraminic acid. Natural substitutions of the basic structure result in over 40 different compounds. Recently, studies of unnatural substitutions have suggested possible innovative approaches to the treatment of a number of human diseases (11, 12, 53, 88).

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